Special Issue "The 10th Anniversary of Antioxidants: Past, Present and Future"

A special issue of Antioxidants (ISSN 2076-3921).

Deadline for manuscript submissions: 31 December 2022 | Viewed by 12918

Special Issue Editors

Prof. Dr. Jiankang Liu
E-Mail Website
Guest Editor
1. School of Health and Life Sciences, University of Health and Rehabilitation Sciences, Qingdao 266071, China
2. School of Life Science and Technology, Xi'an Jiaotong University, Xi'an 710049, China
Interests: aging; age-related diseases; antioxidants; mitochondrial metabolism
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Prof. Dr. Maria Cristina Albertini
E-Mail Website
Guest Editor
Department of Biomolecular Sciences, University of Urbino Carlo Bo, Via Saffi 2, 61029 Urbino, Italy
Interests: molecular pathology; oxidative stress; signal transduction; inflammaging;, microRNAs; bioinfomatics
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Prof. Dr. Yoko Ozawa
E-Mail Website
Guest Editor
1. Department of Ophthalmology, St. Luke's International University and Hospital, Tokyo 104-8560, Japan
2. Department of Ophthalmology, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan
Interests: neuroprotection; retina; vision; oxidative stress; inflammation; aging; age-related macular degeneration; diabetic retinopathy
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Prof. Dr. Dov Lichtenberg
E-Mail Website
Guest Editor
Department of Physiology and Pharmacology, Sackler Medical School, Tel Aviv University, Tel Aviv 6997801, Israel
Interests: physical chemistry of lipids, liposomes, and micelles; detergent solubilization of lipid free radicals; oxidative stress; antioxidants; pro-oxidants
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Prof. Dr. Serkos A. Haroutounian
E-Mail Website
Guest Editor
Laboratory of Nutritional Physiology and Feeding, Department of Animal Science, School of Animal Biosciences, Agricultural University of Athens, Iera Odos 75, GR-11855 Athens, Greece
Interests: bioactive compounds; antioxidants; food additives; natural products; circular economy
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Antioxidants is an international, peer-reviewed, open-access journal published monthly online by MDPI, and published its first Issue in September 2011. After 10 years, Antioxidants has published nearly 3800 papers with the diversity and richness of research in the field of redox biology from basic research to clinical applications. With the enthusiastic and continuous support of the authors, editors, reviewers, and readers, Antioxidants has attained an excellent reputation in the world of science and has successfully risen to be one of the  top 4 journals (Redox Biology, Antioxidants and Redox Signaling, Free Radical Biology and Medicine, Antioxidants) focusing on oxidative stress and antioxidants in health and diseases. Antioxidants does its best to provide scientists with a super-rapid publication process to satisfy the urgent priority of quickly publishing high-quality manuscripts on timely topics. Indeed, a first decision is provided to authors after approximately only 14 days, and acceptance to publication is undertaken in only 3.5 days. The Impact Factor has steadily increased to 6.312 (2020), and its 5-Year Impact Factor has increased to 6.648 (2020). Considering the fierce competition between journals at present, this is a remarkable achievement. Therefore, we would like to put out a Special Issue entitled “The 10th Anniversary of Antioxidants: Past, Present and Future” to celebrate the unparalleled success and the 10th anniversary of Antioxidants. Top experts will be invited to contribute papers to this Special Issue to review past works, demonstrate the present state-of-the-art, and prospect the future of the field of oxidants and antioxidants.

The scope of the Issue includes but is not limited to the following:

  • Basics of oxidants (free radicals and reactive species) and antioxidants: chemistry, biochemistry, physiology, pathology and toxicology, including historical review of the evolution of free radical biology and medicine (redox biology).
  • Redox homeostasis: oxidative stress and antioxidant networks in aging and diseases (inflamm-aging).
  • Methodologies for the quantitation of oxidative stress biomarkers and antioxidant defense system.
  • Low-molecular-weight antioxidants, enzymatic antioxidants, natural and synthetic antioxidants, especially their in vivo metabolism and interactions;
  • Practical applications and limitations of antioxidants: nutrients, drugs, and cosmetics.
  • Novel, smart, autonomous, and intelligent delivery of antioxidants.
  • Perspectives of future trends/directions.

Prof. Dr. Jiankang Liu
Prof. Dr. Maria Cristina Albertini
Prof. Dr. Yoko Ozawa
Prof. Dr. Dov Lichtenberg
Prof. Dr. Serkos A. Haroutounian
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Antioxidants is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2200 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • free radicals
  • antioxidants
  • redox signaling
  • mitochondria
  • natural compounds
  • health and disease

Published Papers (20 papers)

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Research

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Article
Salidroside Ameliorates Radiation Damage by Reducing Mitochondrial Oxidative Stress in the Submandibular Gland
Antioxidants 2022, 11(7), 1414; https://doi.org/10.3390/antiox11071414 - 21 Jul 2022
Viewed by 337
Abstract
Radiotherapy for patients with head and neck cancer inevitably causes radiation damage to salivary glands (SGs). Overproduction of reactive oxygen species (ROS) leads to mitochondrial damage and is critical in the pathophysiology of SG radiation damage. However, mitochondrial-targeted treatment is unavailable. Herein, both [...] Read more.
Radiotherapy for patients with head and neck cancer inevitably causes radiation damage to salivary glands (SGs). Overproduction of reactive oxygen species (ROS) leads to mitochondrial damage and is critical in the pathophysiology of SG radiation damage. However, mitochondrial-targeted treatment is unavailable. Herein, both in vitro and in vivo models of radiation-damaged rat submandibular glands (SMGs) were used to investigate the potential role of salidroside in protecting irradiated SGs. Cell morphology was observed with an inverted phase-contrast microscope. Malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), mitochondrial ROS, mitochondrial membrane potential (MMP), and ATP were measured using relevant kits. The mitochondrial ultrastructure was observed under transmission electron microscopy. Cell apoptosis was determined by Western blot and TUNEL assays. Saliva was measured from Wharton’s duct. We found that salidroside protected SMG cells and tissues against radiation and improved the secretion function. Moreover, salidroside enhanced the antioxidant defense by decreasing MDA, increasing SOD, CAT, and GSH, and scavenging mitochondrial ROS. Furthermore, salidroside rescued the mitochondrial ultrastructure, preserved MMP and ATP, suppressed cytosolic cytochrome c and cleaved caspase 3 expression, and inhibited cell apoptosis. Together, these findings first identify salidroside as a mitochondrial-targeted antioxidant for preventing SG radiation damage. Full article
(This article belongs to the Special Issue The 10th Anniversary of Antioxidants: Past, Present and Future)
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Article
Overexpression of Mitochondrial Ferritin Enhances Blood–Brain Barrier Integrity Following Ischemic Stroke in Mice by Maintaining Iron Homeostasis in Endothelial Cells
Antioxidants 2022, 11(7), 1257; https://doi.org/10.3390/antiox11071257 - 26 Jun 2022
Viewed by 489
Abstract
Blood–brain barrier (BBB) breakdown, a characteristic feature of ischemic stroke, contributes to poor patient outcomes. Brain microvascular endothelial cells (BMVECs) are a key component of the BBB and dysfunction or death of these cells following cerebral ischemia reperfusion (I/R) injury can disrupt the [...] Read more.
Blood–brain barrier (BBB) breakdown, a characteristic feature of ischemic stroke, contributes to poor patient outcomes. Brain microvascular endothelial cells (BMVECs) are a key component of the BBB and dysfunction or death of these cells following cerebral ischemia reperfusion (I/R) injury can disrupt the BBB, leading to leukocyte infiltration, brain edema and intracerebral hemorrhage. We previously demonstrated that mitochondrial ferritin (FtMt) can alleviate I/R-induced neuronal ferroptosis by inhibiting inflammation-regulated iron deposition. However, whether FtMt is involved in BBB disruption during cerebral I/R is still unknown. In the present study, we found that FtMt expression in BMVECs is upregulated after I/R and overexpression of FtMt attenuates I/R-induced BBB disruption. Mechanistically, we found that FtMt prevents tight junction loss and apoptosis by inhibiting iron dysregulation and reactive oxygen species (ROS) accumulation in I/R-treated BMVECs. Chelating excess iron with deferoxamine alleviates apoptosis in the brain endothelial cell line bEnd.3 under oxygen glucose deprivation followed by reoxygenation (OGD/R) insult. In summary, our data identify a previously unexplored effect for FtMt in the BBB and provide evidence that iron-mediated oxidative stress in BMVECs is an early cause of BMVECs damage and BBB breakdown in ischemic stroke. Full article
(This article belongs to the Special Issue The 10th Anniversary of Antioxidants: Past, Present and Future)
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Article
The Use of Quercetin to Improve the Antioxidant and Regenerative Properties of Frozen or Cryopreserved Human Amniotic Membrane
Antioxidants 2022, 11(7), 1250; https://doi.org/10.3390/antiox11071250 - 25 Jun 2022
Viewed by 473
Abstract
The biological properties of the human amniotic membrane (HAM) and its characteristic ability to be a reservoir of growth factors promoting wound healing make it an ideal biological dressing for the treatment of different clinical conditions, such as burns and non-healing wounds. However, [...] Read more.
The biological properties of the human amniotic membrane (HAM) and its characteristic ability to be a reservoir of growth factors promoting wound healing make it an ideal biological dressing for the treatment of different clinical conditions, such as burns and non-healing wounds. However, the application of a preservation method on the HAM is required during banking to maintain biological tissue properties and to ensure the release overtime of protein content for its final clinical effectiveness after application on the wound bed. Although cryopreservation and freezing are methods widely used to maintain tissue properties, reactive oxygen species (ROS) are produced within tissue cellular components during their switching from frozen to thawed state. Consequently, these methods can lead to oxidative stress-induced cell injury, affecting tissue regenerative properties and its final clinical effectiveness. Taking advantage of the antioxidant activity of the natural compound quercetin, we used it to improve the antioxidant and regenerative properties of frozen or cryopreserved HAM tissues. In particular, we evaluated the oxidative damage (lipid peroxidation, malondialdehyde) as well as the regenerative/biological properties (bFGF growth factor release, wound healing closure, structure, and viability) of HAM tissue after its application. We identified the effectiveness of quercetin on both preservation methods to reduce oxidative damage, as well as its ability to enhance regenerative properties, while maintaining the unaltered structure and viability of HAM tissue. The use of quercetin described in this study appears able to counteract the side effects of cryopreservation and freezing methods related to oxidative stress, enhancing the regenerative properties of HAM. However, further investigations will need to be performed, starting from these promising results, to identify its beneficial effect when applied on burns or non-healing wounds. Full article
(This article belongs to the Special Issue The 10th Anniversary of Antioxidants: Past, Present and Future)
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Article
Antioxidant Effect of Tyr-Ala Extracted from Zein on INS-1 Cells and Type 2 Diabetes High-Fat-Diet-Induced Mice
Antioxidants 2022, 11(6), 1111; https://doi.org/10.3390/antiox11061111 - 02 Jun 2022
Viewed by 642
Abstract
Type 2 diabetes mellitus (T2DM) is associated with an oxidative milieu that often leads to adverse health problems. Bioactive peptides of zein possess outstanding antioxidant activity; however, their effects on hyperglycemia-related oxidative stress remain elusive. In the present study, the dipeptide Tyr-Ala (YA), [...] Read more.
Type 2 diabetes mellitus (T2DM) is associated with an oxidative milieu that often leads to adverse health problems. Bioactive peptides of zein possess outstanding antioxidant activity; however, their effects on hyperglycemia-related oxidative stress remain elusive. In the present study, the dipeptide Tyr-Ala (YA), a functional peptide with typical health benefits, was applied to alleviate oxidative stress in pancreatic islets under hyperglycemic conditions. By detecting viability, antioxidant ability, and insulin secretion in INS-1 cells, YA showed excellent protection of INS-1 cells from H2O2 oxidative stress, erasing reactive oxygen species (ROS) and promoting insulin secretion. Moreover, by Western blotting, we found that YA can regulate the PI3K/Akt signaling pathway associated with glycometabolism. After establishing a T2DM mice model, we treated mice with YA and measured glucose, insulin, hemoglobin A1C (HbA1c), total cholesterol (TC), triglyceride (TG), and malonaldehyde (MDA) levels and activities of superoxide dismutase (SOD) and glutathione (GSH) from blood samples. We observed that YA could reduce the production of glucose, insulin, HbA1c, TC, TG, and MDA, in addition to enhancing the activities of SOD and GSH. YA could also repair the function of the kidneys and pancreas of T2DM mice. Along with the decline in fasting blood glucose, the oxidative stress in islets was alleviated in T2DM mice after YA administration. This may improve the health situation of diabetic patients in the future. Full article
(This article belongs to the Special Issue The 10th Anniversary of Antioxidants: Past, Present and Future)
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Article
Curcumin, Polydatin and Quercetin Synergistic Activity Protects from High-Glucose-Induced Inflammation and Oxidative Stress
Antioxidants 2022, 11(6), 1037; https://doi.org/10.3390/antiox11061037 - 24 May 2022
Viewed by 675
Abstract
Chronic hyperglycemia, the diagnostic biomarker of Type 2 Diabetes Mellitus (T2DM), is a condition that fosters oxidative stress and proinflammatory signals, both involved in the promotion of cellular senescence. Senescent cells acquire a proinflammatory secretory phenotype, called SASP, exacerbating and perpetuating the detrimental [...] Read more.
Chronic hyperglycemia, the diagnostic biomarker of Type 2 Diabetes Mellitus (T2DM), is a condition that fosters oxidative stress and proinflammatory signals, both involved in the promotion of cellular senescence. Senescent cells acquire a proinflammatory secretory phenotype, called SASP, exacerbating and perpetuating the detrimental effects of hyperglycemia. Bioactive compounds can exert antioxidant and anti-inflammatory properties. However, the synergistic anti-inflammatory and antioxidant effects of the most extensively investigated natural compounds have not been confirmed yet in senescent cells and in hyperglycemic conditions. Here, we exposed young and replicative senescent HUVEC (yHUVEC and sHUVEC) to a high-glucose (HG) condition (45 mM) and treated them with Polydatin (POL), Curcumin (CUR) and Quercetin (QRC), alone or in combination (MIX), to mirror the anti-inflammatory component OxiDefTM contained in the novel nutraceutical GlicefenTM (Mivell, Italy). In both yHUVEC and sHUVEC, the MIX significantly decreased the expression levels of inflammatory markers, such as MCP-1, IL-1β and IL-8, and ROS production. Importantly, in sHUVEC, a synergistic effect of the MIX was observed, suggesting its senomorphic activity. Moreover, the MIX was able to reduce the expression level of RAGE, a receptor involved in the activation of proinflammatory signaling. Overall, our data suggest that the consumption of nutraceuticals containing different natural compounds could be an adjuvant supplement to counteract proinflammatory and pro-oxidative signals induced by both hyperglycemic and senescence conditions. Full article
(This article belongs to the Special Issue The 10th Anniversary of Antioxidants: Past, Present and Future)
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Article
Identification of Modulators of the C. elegans Aryl Hydrocarbon Receptor and Characterization of Transcriptomic and Metabolic AhR-1 Profiles
Antioxidants 2022, 11(5), 1030; https://doi.org/10.3390/antiox11051030 - 23 May 2022
Viewed by 751
Abstract
The Aryl hydrocarbon Receptor (AhR) is a xenobiotic sensor in vertebrates, regulating the metabolism of its own ligands. However, no ligand has been identified to date for any AhR in invertebrates. In C. elegans, the AhR ortholog, AHR-1, displays physiological functions. [...] Read more.
The Aryl hydrocarbon Receptor (AhR) is a xenobiotic sensor in vertebrates, regulating the metabolism of its own ligands. However, no ligand has been identified to date for any AhR in invertebrates. In C. elegans, the AhR ortholog, AHR-1, displays physiological functions. Therefore, we compared the transcriptomic and metabolic profiles of worms expressing AHR-1 or not and investigated the putative panel of chemical AHR-1 modulators. The metabolomic profiling indicated a role for AHR-1 in amino acids, carbohydrates, and fatty acids metabolism. The transcriptional profiling in neurons expressing AHR-1, identified 95 down-regulated genes and 76 up-regulated genes associated with neuronal and metabolic functions in the nervous system. A gene reporter system allowed us to identify several AHR-1 modulators including bacterial, dietary, or environmental compounds. These results shed new light on the biological functions of AHR-1 in C. elegans and perspectives on the evolution of the AhR functions across species. Full article
(This article belongs to the Special Issue The 10th Anniversary of Antioxidants: Past, Present and Future)
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Article
Phytochemical Characterization, Antioxidant and Anti-Proliferative Properties of Rubia cordifolia L. Extracts Prepared with Improved Extraction Conditions
Antioxidants 2022, 11(5), 1006; https://doi.org/10.3390/antiox11051006 - 20 May 2022
Viewed by 590
Abstract
Rubia cordifolia L. (Rubiaceae) is an important plant in Indian and Chinese medical systems. Extracts prepared from the root, stem and leaf have been used traditionally for the management of various diseases. Some of the known effects are anti-inflammation, neuroprotection, anti-proliferation, immunomodulation and [...] Read more.
Rubia cordifolia L. (Rubiaceae) is an important plant in Indian and Chinese medical systems. Extracts prepared from the root, stem and leaf have been used traditionally for the management of various diseases. Some of the known effects are anti-inflammation, neuroprotection, anti-proliferation, immunomodulation and anti-tumor. A comparative account of the extracts derived from different organs that lead to the identification of the most suitable solvent is lacking. We explored the presence of phytochemicals, antioxidant activity and anti-proliferative properties of a variety of solvent-based extracts of root, and methanol extracts of stem and leaf of R. cordifolia L. The antioxidant potential was determined by DPPH, hydrogen peroxide, nitric oxide and total antioxidant assays. The anti-proliferative nature was evaluated by MTT assay on HeLa, ME-180 and HepG2 cells. The composition of the extracts was determined by UPLC-UV-MS. We found that the root extracts had the presence of higher amounts of antioxidants over the stem and leaf extracts. The root extracts prepared in methanol exhibited the highest cytotoxicity in HepG2 cells. The main compounds identified through UPLC-UV-MS of the methanol extract give credibility to the previous results. Our comprehensive study corroborates the preference given to the root over the stem and leaf for extract preparation. In conclusion, we identified the methanol extract of the root to be the most suited to have bioactivity with anti-cancer potential. Full article
(This article belongs to the Special Issue The 10th Anniversary of Antioxidants: Past, Present and Future)
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Article
Characterization of the Biological Activity of the Ethanolic Extract from the Roots of Cannabis sativa L. Grown in Aeroponics
Antioxidants 2022, 11(5), 860; https://doi.org/10.3390/antiox11050860 - 27 Apr 2022
Viewed by 580
Abstract
Cannabis sativa var. Kompolti, a variety routinely used for food production purposes, is characterized by a low concentration of psychoactive molecules, although containing many other biologically attractive metabolites in all parts of the plant, including the roots. In the present work, we evaluate [...] Read more.
Cannabis sativa var. Kompolti, a variety routinely used for food production purposes, is characterized by a low concentration of psychoactive molecules, although containing many other biologically attractive metabolites in all parts of the plant, including the roots. In the present work, we evaluate the specific biological activities of the roots’ extract from plants cultivated through aeroponics, an affordable and reliable method facilitating the isolation and processing of roots, with the advantage of being suitable for industrial scale-up. Furthermore, aeroponics results in an increased net accumulation of the most biologically attractive constituents (β-sitosterol, friedelin and epi-friedelanol) found in the roots. The ethanolic extract of the aeroponic roots of C. sativa (APEX) and its separate components are studied to evaluate their anti-inflammatory (modulation of the expression level of specific markers upon LPS stimulation in U937 cells, such as IL-6, IL-8, TNF-α, IkB-α, iNOS, IRAK-1 and miR-146a) and antioxidant (in either acellular or cellular settings) activities. The APEX anti-inflammatory and antioxidant capacities are also functionally benchmarked using the wound-healing assay. On the whole, the data obtained show that APEX and its main components showed significant anti-inflammatory and antioxidant activities, which may render the exploitation of roots as a source of natural antioxidants and anti-inflammatory agents highly attractive, with the additional technical and economic advantages of aeroponics compared to soil cultivation. Full article
(This article belongs to the Special Issue The 10th Anniversary of Antioxidants: Past, Present and Future)
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Article
Challenges in Quantifying 8-OHdG and 8-Isoprostane in Exhaled Breath Condensate
Antioxidants 2022, 11(5), 830; https://doi.org/10.3390/antiox11050830 - 25 Apr 2022
Viewed by 505
Abstract
Exhaled breath condensate (EBC) has attracted substantial interest in the last few years, enabling the assessment of airway inflammation with a non-invasive method. Concentrations of 8-Hydroxydesoxyguanosine (8-OHdG) and 8-isoprostane in EBC have been suggested as candidate biomarkers for lung diseases associated with inflammation [...] Read more.
Exhaled breath condensate (EBC) has attracted substantial interest in the last few years, enabling the assessment of airway inflammation with a non-invasive method. Concentrations of 8-Hydroxydesoxyguanosine (8-OHdG) and 8-isoprostane in EBC have been suggested as candidate biomarkers for lung diseases associated with inflammation and oxidative stress. EBC is a diluted biological matrix and consequently, requires highly sensitive chemical analytic methods (picomolar range) for biomarker quantification. We developed a new liquid chromatography coupled to tandem mass spectrometry method to quantify 8-OHdG and 8-isoprostane in EBC simultaneously. We applied this novel biomarker method in EBC obtained from 10 healthy subjects, 7 asthmatic subjects, and 9 subjects with chronic obstructive pulmonary disease. Both biomarkers were below the limit of detection (LOD) despite the good sensitivity of the chemical analytical method (LOD = 0.5 pg/mL for 8-OHdG; 1 pg/mL for 8-isoprostane). This lack of detection might result from factors affecting EBC collections. These findings are in line with methodological concerns already raised regarding the reliability of EBC collection for quantification of 8-OHdG and 8-isoprostane. Precaution is therefore needed when comparing literature results without considering methodological issues relative to EBC collection and analysis. Loss of analyte during EBC collection procedures still needs to be resolved before using these oxidative stress biomarkers in EBC. Full article
(This article belongs to the Special Issue The 10th Anniversary of Antioxidants: Past, Present and Future)
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Article
Pre-Operative Assessment of Micronutrients, Amino Acids, Phospholipids and Oxidative Stress in Bariatric Surgery Candidates
Antioxidants 2022, 11(4), 774; https://doi.org/10.3390/antiox11040774 - 13 Apr 2022
Viewed by 609
Abstract
Obesity has been linked to lower concentrations of fat-soluble micronutrients and higher concentrations of oxidative stress markers as well as an altered metabolism of branched chain amino acids and phospholipids. In the context of morbid obesity, the aim of this study was to [...] Read more.
Obesity has been linked to lower concentrations of fat-soluble micronutrients and higher concentrations of oxidative stress markers as well as an altered metabolism of branched chain amino acids and phospholipids. In the context of morbid obesity, the aim of this study was to investigate whether and to which extent plasma status of micronutrients, amino acids, phospholipids and oxidative stress differs between morbidly obese (n = 23) and non-obese patients (n = 13). In addition to plasma, malondialdehyde, retinol, cholesterol and triglycerides were assessed in visceral and subcutaneous adipose tissue in both groups. Plasma γ-tocopherol was significantly lower (p < 0.011) in the obese group while other fat-soluble micronutrients showed no statistically significant differences between both groups. Branched-chain amino acids (all p < 0.008) and lysine (p < 0.006) were significantly higher in morbidly obese patients compared to the control group. Malondialdehyde concentrations in both visceral (p < 0.016) and subcutaneous (p < 0.002) adipose tissue were significantly higher in the morbidly obese group while plasma markers of oxidative stress showed no significant differences between both groups. Significantly lower plasma concentrations of phosphatidylcholine, phosphatidylethanolamine, lyso-phosphatidylethanolamine (all p < 0.05) and their corresponding ether-linked analogs were observed, which were all reduced in obese participants compared to the control group. Pre-operative assessment of micronutrients in patients undergoing bariatric surgery is recommended for early identification of patients who might be at higher risk to develop a severe micronutrient deficiency post-surgery. Assessment of plasma BCAAs and phospholipids in obese patients might help to differentiate between metabolic healthy patients and those with metabolic disorders. Full article
(This article belongs to the Special Issue The 10th Anniversary of Antioxidants: Past, Present and Future)
Article
α-Acylamino-β-lactone N-Acylethanolamine-hydrolyzing Acid Amidase Inhibitors Encapsulated in PLGA Nanoparticles: Improvement of the Physical Stability and Protection of Human Cells from Hydrogen Peroxide-Induced Oxidative Stress
Antioxidants 2022, 11(4), 686; https://doi.org/10.3390/antiox11040686 - 31 Mar 2022
Cited by 2 | Viewed by 541
Abstract
N-Acylethanolamine acid amidase (NAAA) is an N-terminal cysteine hydrolase that preferentially catalyzes the hydrolysis of endogenous lipid mediators such as palmitoylethanolamide, which has been shown to exhibit neuroprotective and antinociceptive properties by engaging peroxisome proliferator-activated receptor-α. A few potent NAAA inhibitors have [...] Read more.
N-Acylethanolamine acid amidase (NAAA) is an N-terminal cysteine hydrolase that preferentially catalyzes the hydrolysis of endogenous lipid mediators such as palmitoylethanolamide, which has been shown to exhibit neuroprotective and antinociceptive properties by engaging peroxisome proliferator-activated receptor-α. A few potent NAAA inhibitors have been developed, including α-acylamino-β-lactone derivatives, which are very strong and effective, but they have limited chemical and plasmatic stability, compromising their use as systemic agents. In the present study, as an example of a molecule belonging to the chemical class of N-(2-oxo-3-oxetanyl)amide NAAA inhibitors, URB866 was entrapped in poly(lactic-co-glycolic acid) nanoparticles in order to increase its physical stability. The data show a monomodal pattern and a significant time- and temperature-dependent stability of the molecule-loaded nanoparticles, which also demonstrated a greater ability to effectively retain the compound. The nanoparticles improved the photostability of URB866 with respect to that of the free molecule and displayed a better antioxidant profile on various cell lines at the molecule concentration of 25 μM. Overall, these results prove that the use of polymeric nanoparticles could be a useful strategy for overcoming the instability of α-acylamino-β-lactone NAAA inhibitors, allowing the maintenance of their characteristics and activity for a longer time. Full article
(This article belongs to the Special Issue The 10th Anniversary of Antioxidants: Past, Present and Future)
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Article
Aryl Hydrocarbon Receptor-Dependent and -Independent Pathways Mediate Curcumin Anti-Aging Effects
Antioxidants 2022, 11(4), 613; https://doi.org/10.3390/antiox11040613 - 23 Mar 2022
Viewed by 685
Abstract
The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor whose activity can be modulated by polyphenols, such as curcumin. AhR and curcumin have evolutionarily conserved effects on aging. Here, we investigated whether and how the AhR mediates the anti-aging effects of curcumin [...] Read more.
The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor whose activity can be modulated by polyphenols, such as curcumin. AhR and curcumin have evolutionarily conserved effects on aging. Here, we investigated whether and how the AhR mediates the anti-aging effects of curcumin across species. Using a combination of in vivo, in vitro, and in silico analyses, we demonstrated that curcumin has AhR-dependent or -independent effects in a context-specific manner. We found that in Caenorhabditis elegans, AhR mediates curcumin-induced lifespan extension, most likely through a ligand-independent inhibitory mechanism related to its antioxidant activity. Curcumin also showed AhR-independent anti-aging activities, such as protection against aggregation-prone proteins and oxidative stress in C. elegans and promotion of the migratory capacity of human primary endothelial cells. These AhR-independent effects are largely mediated by the Nrf2/SKN-1 pathway. Full article
(This article belongs to the Special Issue The 10th Anniversary of Antioxidants: Past, Present and Future)
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Review

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Review
Oxidative Stress: What Is It? Can It Be Measured? Where Is It Located? Can It Be Good or Bad? Can It Be Prevented? Can It Be Cured?
Antioxidants 2022, 11(8), 1431; https://doi.org/10.3390/antiox11081431 - 23 Jul 2022
Viewed by 359
Abstract
The meaning, the appropriate usage and the misusage of the terms oxidative stress, oxidative eustress, and oxidative distress have been evaluated. It has been realized that the terms oxidative stress and oxidative damage are often used inappropriately as synonyms. The usage of the [...] Read more.
The meaning, the appropriate usage and the misusage of the terms oxidative stress, oxidative eustress, and oxidative distress have been evaluated. It has been realized that the terms oxidative stress and oxidative damage are often used inappropriately as synonyms. The usage of the term eustress (intended as good stress) is unsuitable to indicate signaling by reactive molecular an event that can be finalistically considered either good or bad, depending on the circumstances. The so defined oxidative distress is an oxidative damage but not an oxidative stress. What is measured and defined as oxidative stress is in fact an oxidative damage. Damaging oxidations and signaling oxidant events (good or bad) can be present, also simultaneously, in different and multiple location of a cell, tissue or body and the measure of an oxidant event in body fluids or tissue specimen can only be the sum of non-separatable events, sometimes of opposite sign. There is no officially approved therapy to prevent or cure oxidative stress or oxidative damage. Full article
(This article belongs to the Special Issue The 10th Anniversary of Antioxidants: Past, Present and Future)
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Review
What Are the Oxidizing Intermediates in the Fenton and Fenton-like Reactions? A Perspective
Antioxidants 2022, 11(7), 1368; https://doi.org/10.3390/antiox11071368 - 14 Jul 2022
Viewed by 357
Abstract
The Fenton and Fenton-like reactions are of major importance due to their role as a source of oxidative stress in all living systems and due to their use in advanced oxidation technologies. For many years, there has been a debate whether the reaction [...] Read more.
The Fenton and Fenton-like reactions are of major importance due to their role as a source of oxidative stress in all living systems and due to their use in advanced oxidation technologies. For many years, there has been a debate whether the reaction of FeII(H2O)62+ with H2O2 yields OH radicals or FeIV=Oaq. It is now known that this reaction proceeds via the formation of the intermediate complex (H2O)5FeII(O2H)+/(H2O)5FeII(O2H2)2+ that decomposes to form either OH radicals or FeIV=Oaq, depending on the pH of the medium. The intermediate complex might also directly oxidize a substrate present in the medium. In the presence of FeIIIaq, the complex FeIII(OOH)aq is formed. This complex reacts via FeII(H2O)62+ + FeIII(OOH)aq → FeIV=Oaq + FeIIIaq. In the presence of ligands, the process often observed is Ln(H2O)5−nFeII(O2H) → L+ + Ln−1FeIIIaq. Thus, in the presence of small concentrations of HCO3 i.e., in biological systems and in advanced oxidation processes—the oxidizing radical formed is CO3. It is evident that, in the presence of other transition metal complexes and/or other ligands, other radicals might be formed. In complexes of the type Ln(H2O)5−nMIII/II(O2H), the peroxide might oxidize the ligand L without oxidizing the central cation M. OH radicals are evidently not often formed in Fenton or Fenton-like reactions. Full article
(This article belongs to the Special Issue The 10th Anniversary of Antioxidants: Past, Present and Future)
Review
How Aging and Oxidative Stress Influence the Cytopathic and Inflammatory Effects of SARS-CoV-2 Infection: The Role of Cellular Glutathione and Cysteine Metabolism
Antioxidants 2022, 11(7), 1366; https://doi.org/10.3390/antiox11071366 - 14 Jul 2022
Viewed by 570
Abstract
SARS-CoV-2 infection can cause a severe respiratory distress syndrome with inflammatory and thrombotic complications, the severity of which increases with patients’ age and presence of comorbidity. The reasons for an age-dependent increase in the risk of severe COVID-19 could be many. These include [...] Read more.
SARS-CoV-2 infection can cause a severe respiratory distress syndrome with inflammatory and thrombotic complications, the severity of which increases with patients’ age and presence of comorbidity. The reasons for an age-dependent increase in the risk of severe COVID-19 could be many. These include defects in the homeostatic processes that control the cellular redox and its pivotal role in sustaining the immuno-inflammatory response to the host and the protection against oxidative stress and tissue degeneration. Pathogens may take advantage of such age-dependent abnormalities. Alterations of the thiol redox balance in the lung tissue and lining fluids may influence the risk of infection, and the host capability to respond to pathogens and to avoid severe complications. SARS-CoV-2, likewise other viruses, such as HIV, influenza, and HSV, benefits in its replication cycle of pro-oxidant conditions that the same viral infection seems to induce in the host cell with mechanisms that remain poorly understood. We recently demonstrated that the pro-oxidant effects of SARS-CoV-2 infection are associated with changes in the cellular metabolism and transmembrane fluxes of Cys and GSH. These appear to be the consequence of an increased use of Cys in viral protein synthesis and to ER stress pathway activation that interfere with transcription factors, as Nrf2 and NFkB, important to coordinate the metabolism of GSH with other aspects of the stress response and with the pro-inflammatory effects of this virus in the host cell. This narrative review article describes these cellular and molecular aspects of SARS-CoV-2 infection, and the role that antivirals and cytoprotective agents such as N-acetyl cysteine may have to limit the cytopathic effects of this virus and to recover tissue homeostasis after infection. Full article
(This article belongs to the Special Issue The 10th Anniversary of Antioxidants: Past, Present and Future)
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Review
Oxidative Stress in Type 2 Diabetes: The Case for Future Pediatric Redoxomics Studies
Antioxidants 2022, 11(7), 1336; https://doi.org/10.3390/antiox11071336 - 07 Jul 2022
Viewed by 444
Abstract
Considerable evidence supports the role of oxidative stress in adult type 2 diabetes (T2D). Due to increasing rates of pediatric obesity, lack of physical activity, and consumption of excess food calories, it is projected that the number of children living with insulin resistance, [...] Read more.
Considerable evidence supports the role of oxidative stress in adult type 2 diabetes (T2D). Due to increasing rates of pediatric obesity, lack of physical activity, and consumption of excess food calories, it is projected that the number of children living with insulin resistance, prediabetes, and T2D will markedly increase with enormous worldwide economic costs. Understanding the factors contributing to oxidative stress and T2D risk may help develop optimal early intervention strategies. Evidence suggests that oxidative stress, triggered by excess dietary fat consumption, causes excess mitochondrial hydrogen peroxide emission in skeletal muscle, alters redox status, and promotes insulin resistance leading to T2D. The pathophysiological events arising from excess calorie-induced mitochondrial reactive oxygen species production are complex and not yet investigated in children. Systems medicine is an integrative approach leveraging conventional medical information and environmental factors with data obtained from “omics” technologies such as genomics, proteomics, and metabolomics. In adults with T2D, systems medicine shows promise in risk assessment and predicting drug response. Redoxomics is a branch of systems medicine focusing on “omics” data related to redox status. Systems medicine with a complementary emphasis on redoxomics can potentially optimize future healthcare strategies for adults and children with T2D. Full article
(This article belongs to the Special Issue The 10th Anniversary of Antioxidants: Past, Present and Future)
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Review
Metabolic Adaptation-Mediated Cancer Survival and Progression in Oxidative Stress
Antioxidants 2022, 11(7), 1324; https://doi.org/10.3390/antiox11071324 - 05 Jul 2022
Viewed by 480
Abstract
Undue elevation of ROS levels commonly occurs during cancer evolution as a result of various antitumor therapeutics and/or endogenous immune response. Overwhelming ROS levels induced cancer cell death through the dysregulation of ROS-sensitive glycolytic enzymes, leading to the catastrophic depression of glycolysis and [...] Read more.
Undue elevation of ROS levels commonly occurs during cancer evolution as a result of various antitumor therapeutics and/or endogenous immune response. Overwhelming ROS levels induced cancer cell death through the dysregulation of ROS-sensitive glycolytic enzymes, leading to the catastrophic depression of glycolysis and oxidative phosphorylation (OXPHOS), which are critical for cancer survival and progression. However, cancer cells also adapt to such catastrophic oxidative and metabolic stresses by metabolic reprograming, resulting in cancer residuality, progression, and relapse. This adaptation is highly dependent on NADPH and GSH syntheses for ROS scavenging and the upregulation of lipolysis and glutaminolysis, which fuel tricarboxylic acid cycle-coupled OXPHOS and biosynthesis. The underlying mechanism remains poorly understood, thus presenting a promising field with opportunities to manipulate metabolic adaptations for cancer prevention and therapy. In this review, we provide a summary of the mechanisms of metabolic regulation in the adaptation of cancer cells to oxidative stress and the current understanding of its regulatory role in cancer survival and progression. Full article
(This article belongs to the Special Issue The 10th Anniversary of Antioxidants: Past, Present and Future)
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Review
Antioxidant Therapy in Cancer: Rationale and Progress
Antioxidants 2022, 11(6), 1128; https://doi.org/10.3390/antiox11061128 - 08 Jun 2022
Viewed by 625
Abstract
Cancer is characterized by increased oxidative stress, an imbalance between reactive oxygen species (ROS) and antioxidants. Enhanced ROS accumulation, as a result of metabolic disturbances and signaling aberrations, can promote carcinogenesis and malignant progression by inducing gene mutations and activating pro-oncogenic signaling, providing [...] Read more.
Cancer is characterized by increased oxidative stress, an imbalance between reactive oxygen species (ROS) and antioxidants. Enhanced ROS accumulation, as a result of metabolic disturbances and signaling aberrations, can promote carcinogenesis and malignant progression by inducing gene mutations and activating pro-oncogenic signaling, providing a possible rationale for targeting oxidative stress in cancer treatment. While numerous antioxidants have demonstrated therapeutic potential, their clinical efficacy in cancer remains unproven. Here, we review the rationale for, and recent advances in, pre-clinical and clinical research on antioxidant therapy in cancer, including targeting ROS with nonenzymatic antioxidants, such as NRF2 activators, vitamins, N-acetylcysteine and GSH esters, or targeting ROS with enzymatic antioxidants, such as NOX inhibitors and SOD mimics. In addition, we will offer insights into prospective therapeutic options for improving the effectiveness of antioxidant therapy, which may expand its applications in clinical cancer treatment. Full article
(This article belongs to the Special Issue The 10th Anniversary of Antioxidants: Past, Present and Future)
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Review
Oxidation of Polyunsaturated Fatty Acids as a Promising Area of Research in Infertility
Antioxidants 2022, 11(5), 1002; https://doi.org/10.3390/antiox11051002 - 19 May 2022
Viewed by 485
Abstract
In this review, the role of fatty acids (FA) in human pathological conditions, infertility in particular, was considered. FA and FA-derived metabolites modulate cell membrane composition, membrane lipid microdomains and cell signaling. Moreover, such molecules are involved in cell death, immunological responses and [...] Read more.
In this review, the role of fatty acids (FA) in human pathological conditions, infertility in particular, was considered. FA and FA-derived metabolites modulate cell membrane composition, membrane lipid microdomains and cell signaling. Moreover, such molecules are involved in cell death, immunological responses and inflammatory processes. Human health and several pathological conditions are specifically associated with both dietary and cell membrane lipid profiles. The role of FA metabolism in human sperm and spermatogenesis has recently been investigated. Cumulative findings indicate F2 isoprostanes (oxygenated products from arachidonic acid metabolism) and resolvins (lipid mediators of resolution of inflammation) as promising biomarkers for the evaluation of semen and follicular fluid quality. Advanced knowledge in this field could lead to new scenarios in the treatment of infertility. Full article
(This article belongs to the Special Issue The 10th Anniversary of Antioxidants: Past, Present and Future)
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Review
Punicalagin Regulates Signaling Pathways in Inflammation-Associated Chronic Diseases
Antioxidants 2022, 11(1), 29; https://doi.org/10.3390/antiox11010029 - 24 Dec 2021
Viewed by 1224
Abstract
Inflammation is a complex biological defense system associated with a series of chronic diseases such as cancer, arthritis, diabetes, cardiovascular and neurodegenerative diseases. The extracts of pomegranate fruit and peel have been reported to possess health-beneficial properties in inflammation-associated chronic diseases. Punicalagin is [...] Read more.
Inflammation is a complex biological defense system associated with a series of chronic diseases such as cancer, arthritis, diabetes, cardiovascular and neurodegenerative diseases. The extracts of pomegranate fruit and peel have been reported to possess health-beneficial properties in inflammation-associated chronic diseases. Punicalagin is considered to be the major active component of pomegranate extracts. In this review we have focused on recent studies into the therapeutic effects of punicalagin on inflammation-associated chronic diseases and the regulatory roles in NF-κB, MAPK, IL-6/JAK/STAT3 and PI3K/Akt/mTOR signaling pathways. We have concluded that punicalagin may be a promising therapeutic compound in preventing and treating inflammation-associated chronic diseases, although further clinical studies are required. Full article
(This article belongs to the Special Issue The 10th Anniversary of Antioxidants: Past, Present and Future)
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Planned Papers

The below list represents only planned manuscripts. Some of these manuscripts have not been received by the Editorial Office yet. Papers submitted to MDPI journals are subject to peer-review.

Title: New insight into Nrf2-pathway modulation by main antioxidant phytochemicals of P. spinosa L. (Rosaceae) fruit extract: integrated bioinformatics analysis and experimental validation
Authors: Maria Cristina Albertini
Affiliation: Department of Biomolecular Sciences, University of Urbino Carlo Bo, Via Saffi 2, 61029 Urbino, Italy

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